8-55161765-C-A

Position:

• chr8-55161765-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052898.2(XKR4):​c.806+58471C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 369,834 control chromosomes in the GnomAD database, including 16,482 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8577 hom., cov: 32)
  • Exomes 𝑓: 0.26 (7905 hom.)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253857 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR4	NM_052898.2	c.806+58471C>A		intron_variant		ENST00000327381.7	NP_443130.1
LOC105375844	NR_188097.1	n.190+121C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.806+58471C>A		intron_variant		1	NM_052898.2	ENSP00000328326.5
ENSG00000253857	ENST00000522559.1	n.162+121C>A		intron_variant		2
ENSG00000253857	ENST00000668329.1	n.199+121C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48990 AN: 151970 Hom.: 8563 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.262 AC: 57050 AN: 217746 Hom.: 7905 AF XY: 0.261 AC XY: 31713 AN XY: 121396

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.322 AC: 49032 AN: 152088 Hom.: 8577 Cov.: 32 AF XY: 0.323 AC XY: 24043 AN XY: 74358

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.312

Alfa AF: 0.200 Hom.: 628

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7837220; hg19: chr8-56074325;